tbuckley/cabot-search huggingface dataset:
Plasma Metabolomics Reveals Distinct Biological and Diagnostic Signatures for Melioidosis
Authors: Lu Xia, Viriya Hantrakun, Prapit Teparrukkul, Gumphol Wongsuvan, Taniya Kaewarpai, Adul Dulsuk, Nicholas P. J. Day, Rozenn N. Lemaitre, Narisara Chantratita, Direk Limmathurotsakul, Ali Shojaie, Sina A. Gharib, T. Eoin West
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: The global burden of sepsis is greatest in low-resource settings. Melioidosis, infection with the gram-negative bacterium Burkholderia pseudomallei, is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia. Objectives: To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers. Methods: Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to patients with melioidosis and between fatal and nonfatal cases. Measurements and Main Results: Metabolomic profiling and pathway enrichment analysis of plasma samples from patients with melioidosis (n = 175) and nonmelioidosis infections (n = 75) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis nonsurvivors (n = 94) had a significantly disturbed metabolome compared with survivors (n = 81), with increased leucine, isoleucine, and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited eight-metabolite panel showed promise as an early prognosticator of mortality in melioidosis. Conclusions: Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A 12-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.
Self‐Luminous Probe with One‐Step Energy Conversion from Bioluminescence to NIR‐IIb
Authors: Zhao Jiang, Zhiwen Yang, Wanwan Li
Journal: Advanced Healthcare Materials (2023)

Self-luminous probes with near-infrared (NIR) emission are powerful tools for deep-penetration and autofluorescence-free imaging, owing to the joint optimization of both excitation and emission. However, the limited emission wavelength and requirement for multistep energy transfer limit its potency. In this study, the concept of direct wavelength conversion is established from visible light (vis) to NIR-IIb using an exquisitely designed sensitizer-activator ion pair. The manipulation of the doping hosts enables a pair of energy levels between the sensitizer and activator. Based on this a class of broadband vis-responsive nanocrystals with intense NIR-II emission is prepared. The stability and quantum yield (up to 7.4%) of the nanocrystals are further enhanced by ZnS passivation via coherent epitaxial growth. By coupling luciferase, the self-luminous probe can convert bioluminescence to NIR-IIb luminescence (>1500 nm) through a one-step energy transfer. A maximum penetrable thickness of 6 mm is achieved in the porcine tissue model. Collectively, the distinctive photon-conversion performance of this probe offers the prospect of high-resolution labeling of deep-seated lesions.
Implications of the Use of Artificial Intelligence Predictive Models in Health Care Settings
Authors: Akhil Vaid, Ashwin Sawant, Mayte Suarez-Farinas, Juhee Lee, Sanjeev Kaul, Patricia Kovatch, Robert Freeman, Joy Jiang, Pushkala Jayaraman, Zahi Fayad, Edgar Argulian, Stamatios Lerakis, Alexander W. Charney, Fei Wang, Matthew Levin, Benjamin Glicksberg, Jagat Narula, Ira Hofer, Karandeep Singh, Girish N. Nadkarni
Journal: Annals of Internal Medicine (2023)

Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and future models.
The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial
Authors: Paula K. Schweitzer, Luigi Taranto-Montemurro, Joseph M. Ojile, Stephen G. Thein, Christopher L. Drake, Russell Rosenberg, Bruce Corser, Brian Abaluck, R. Bart Sangal, James Maynard
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Obstructive sleep apnea (OSA) is a common sleep disorder for which the principal treatment option, continuous positive airway pressure, is often poorly tolerated. There is currently no approved pharmacotherapy for OSA. However, recent studies have demonstrated improvement in OSA with combined antimuscarinic and noradrenergic drugs. Objectives: The aim of this study was to evaluate the efficacy and safety of AD109, a combination of the novel antimuscarinic agent aroxybutynin and the norepinephrine reuptake inhibitor atomoxetine, in the treatment of OSA. Methods: Phase II randomized, double-blind, placebo-controlled, parallel-group, 4-week trial comparing AD109 2.5/75 mg, AD109 5/75 mg, atomoxetine 75 mg alone, and placebo (www.clinicaltrials.gov identifier NCT 05071612). Measurements and Main Results: Of 211 randomized patients, 181 were included in the prespecified efficacy analyses. Sleep was assessed by two baseline and two treatment polysomnograms. Apnea–hypopnea index with a 4% desaturation criterion (primary outcome) was reduced from a median (IQR) of 20.5 (12.3–27.2) to 10.8 (5.6–18.5) in the AD109 2.5/75 mg arm (−47.1%), from 19.4 (13.7–26.4) to 9.5 (6.1–19.3) in the AD109 5/75 mg arm (−42.9%; both P < 0.0001 vs. placebo), and from 19.0 (11.8–28.8) to 11.8 (5.5–21.5) with atomoxetine alone (−38.8%; P < 0.01 vs. placebo). Apnea–hypopnea index with a 4% desaturation criterion decreased from 20.1 (11.9–25.9) to 16.3 (11.1–28.9) in the placebo arm. Subjectively, there was improvement in fatigue with AD109 2.5/75 mg (P < 0.05 vs. placebo and atomoxetine). Atomoxetine taken alone decreased total sleep time (P < 0.05 vs. AD109 and placebo). The most common adverse events were dry mouth, insomnia, and urinary hesitancy. Conclusions: AD109 showed clinically meaningful improvement in OSA, suggesting that further development of the compound is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 05071612).
Xylazine Adulteration of the Heroin–Fentanyl Drug Supply
Authors: Joseph D’Orazio, Lewis Nelson, Jeanmarie Perrone, Rachel Wightman, Rachel Haroz
Journal: Annals of Internal Medicine (2023)

Xylazine is an animal sedative, approved by the U.S. Food and Drug Administration, that is commonly used in veterinary medicine and is not approved for human use. Since 2016, xylazine has consistently appeared in the illicitly manufactured fentanyl supply and has significantly increased in prevalence, likely due to its low cost, easy availability, and presumed synergistic psychoactive effect. Clinical experience along with the available pertinent research were used to review xylazine adulteration of the drug supply and provide guidance on the care of patients exposed to xylazine. This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds.
Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies
Authors: Wenxin Wan, Susan Peters, Lützen Portengen, Ann Olsson, Joachim Schüz, Wolfgang Ahrens, Miriam Schejbalova, Paolo Boffetta, Thomas Behrens, Thomas Brüning, Benjamin Kendzia, Dario Consonni, Paul A. Demers, Eleonóra Fabiánová, Guillermo Fernández-Tardón, John K. Field, Francesco Forastiere, Lenka Foretova, Pascal Guénel, Per Gustavsson, Karl-Heinz Jöckel, Stefan Karrasch, Maria Teresa Landi, Jolanta Lissowska, Christine Barul, Dana Mates, John R. McLaughlin, Franco Merletti, Enrica Migliore, Lorenzo Richiardi, Tamás Pándics, Hermann Pohlabeln, Jack Siemiatycki, Beata Świątkowska, Heinz-Erich Wichmann, David Zaridze, Calvin Ge, Kurt Straif, Hans Kromhout, Roel Vermeulen
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer.
COVID-19
Authors: Kristen M. Marks, Roy M. Gulick
Journal: Annals of Internal Medicine (2023)

COVID-19, the illness caused by SARS-CoV-2, became a worldwide pandemic in 2020. Initial clinical manifestations range from asymptomatic infection to mild upper respiratory illness but may progress to pulmonary involvement with hypoxemia and, in some cases, multiorgan involvement, shock, and death. Older adults, pregnant persons, those with common comorbidities, and those with immunosuppression are at greatest risk for progression. Vaccination is effective in preventing symptomatic infection and reducing risk for severe disease, hospitalization, and death. Antiviral treatment and immunomodulators have been shown to benefit certain patients. This article summarizes current recommendations on prevention, diagnosis, management, and treatment of COVID-19.
Annals Graphic Medicine - The Substance Use Epidemic: A Graphic Narrative
Authors: Arun Thekkekarott Kuruvila, Erin Brender
Journal: Annals of Internal Medicine (2023)

Web Exclusives10 October 2023Annals Graphic Medicine - The Substance Use Epidemic: A Graphic NarrativeFREEArun Thekkekarott Kuruvila, MBBS, MD, and Erin Brender, MDArun Thekkekarott Kuruvila, MBBS, MDAsante Rogue Regional Medical Center, Medford, Oregon (A.T.K., E.B.)Search for more papers by this author, and Erin Brender, MDAsante Rogue Regional Medical Center, Medford, Oregon (A.T.K., E.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0069 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Arun Thekkekarott Kuruvila, MBBS, MD; Erin Brender, MDAffiliations: Asante Rogue Regional Medical Center, Medford, Oregon (A.T.K., E.B.)Disclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0069.Author/Illustrator Information: Arun Thekkekarott Kuruvila, MBBS, MD, is a hospitalist in Oregon and an acclaimed artist who has displayed his artwork at high-quality exhibitions in India and the United States (e-mail, aruntkuruvila@gmail.com). Erin Brender, MD, MRCP (London), is a hospitalist and is leading the Hospital-Based Opioid Treatment initiative in southern Oregon (e-mail, erin.brender@sohpc.com).This article was published at Annals.org on 10 October 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics October 2023Volume 176, Issue 10 ePublished: 10 October 2023 Issue Published: October 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Would You Screen This Patient for Cognitive Impairment?
Authors: Risa B. Burns, Michael J. Barry, Deborah Blacker, Zahir Kanjee
Journal: Annals of Internal Medicine (2023)

Dementia, according to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is defined by a significant decline in 1 or more cognitive domains that interferes with a person's independence in daily activities. Mild cognitive impairment (MCI) differs from dementia in that the impairment is not sufficient to interfere with independence. For the purposes of this discussion, cognitive impairment (CI) includes both dementia and MCI. Various screening tests are available for CI. These tests ask patients to perform a series of tasks that assess 1 or more domains of cognitive function or ask a caregiver to report on the patient's abilities. A positive result on a screening test does not equate to a diagnosis of CI; rather, it should lead to additional testing to confirm the diagnosis. On review of the evidence, the U.S. Preventive Services Task Force (USPSTF) concluded in 2020 that the evidence was insufficient to assess the balance of benefits and harms of screening for CI in older adults ("I statement"). The USPSTF did clarify that although there is insufficient evidence, there may be important reasons to identify CI. In this article, 2 experts review the available evidence to answer the following questions: What screening tools are available, and how effective are they in identifying patients with CI? What interventions are available for patients found to have CI, to what extent do they improve patient outcomes, and what, if any, negative effects occur? And, would they recommend screening for CI, and why or why not?
Risk for Congenital Anomalies in Children Conceived With Medically Assisted Fertility Treatment
Authors: Christos Venetis, Stephanie K.Y. Choi, Louisa Jorm, Xian Zhang, William Ledger, Kei Lui, Alys Havard, Michael Chapman, Robert J. Norman, Georgina M. Chambers
Journal: Annals of Internal Medicine (2023)

Background: More than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation. Objective: To investigate the role of underlying infertility and fertility treatment on CA risks in the first 2 years of life. Design: Propensity score–weighted population-based cohort study. Setting: New South Wales, Australia. Participants: 851 984 infants (828 099 singletons and 23 885 plural children) delivered between 2009 and 2017. Measurements: Adjusted risk difference (aRD) in CAs of infants conceived through fertility treatment compared with 2 naturally conceived (NC) control groups—those with and without a parental history of infertility (NC-infertile and NC-fertile). Results: The overall incidence of CAs was 459 per 10 000 singleton births and 757 per 10 000 plural births. Compared with NC-fertile singleton control infants (n = 747 018), ART-conceived singleton infants (n = 31 256) had an elevated risk for major genitourinary abnormalities (aRD, 19.0 cases per 10 000 births [95% CI, 2.3 to 35.6]); the risk remained unchanged (aRD, 22 cases per 10 000 births [CI, 4.6 to 39.4]) when compared with NC-infertile singleton control infants (n = 36 251) (that is, after accounting for parental infertility), indicating that ART remained an independent risk. After accounting for parental infertility, ICSI in couples without male infertility was associated with an increased risk for major genitourinary abnormalities (aRD, 47.8 cases per 10 000 singleton births [CI, 12.6 to 83.1]). There was some suggestion of increased risk for CAs after fresh embryo transfer, although estimates were imprecise and inconsistent. There were no increased risks for CAs among OI/IUI-conceived infants (n = 13 574). Limitations: This study measured the risk for CAs only in those children who were born at or after 20 weeks' gestation. Observational study design precludes causal inference. Many estimates were imprecise. Conclusion: Patients should be counseled on the small increased risk for genitourinary abnormalities after ART, particularly after ICSI, which should be avoided in couples without problems of male infertility. Primary Funding Source: Australian National Health and Medical Research Council.
Management of Metastatic Renal Clear Cell Cancer: ASCO Guideline Rapid Recommendation Update
Authors: Eric A. Singer, R. Bryan Rumble, W. Kimryn Rathmell, Peter J. Van Veldhuizen, W. Kimryn Rathmell, Peter J. Van Veldhuizen, R. Bryan Rumble, Hikmat Al-Ahmadie, Hamid Emamekhoo, Ralph J. Hauke, Alexander V. Louie, Matthew I. Milowsky, Ana M. Molina, Tracy L. Rose, Shankar Siva, Nicholas G. Zaorsky, Tian Zhang, Rubina Qamar, Terry M. Kungel, Bryan Lewis, Eric A. Singer
Journal: Journal of Clinical Oncology (2023)

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in theASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).
Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment
Authors: Lin Zhang, Jin‐Mei Fu, Lai‐Bo Song, Kai Cheng, Fang Zhang, Wen‐Hui Tan, Jin‐Xuan Fan, Yuan‐Di Zhao
Journal: Advanced Healthcare Materials (2023)

Abstract Multi‐modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super‐small bismuth/copper‐gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co‐encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor‐bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H 2 O 2 ), which reacts with copper ions (Cu 2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O 2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low‐temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi‐modal anticancer therapy.
Surface and Global Proteome Analyses Identify ENPP1 and Other Surface Proteins as Actionable Immunotherapeutic Targets in Ewing Sarcoma
Authors: Brian Mooney, Gian Luca Negri, Taras Shyp, Alberto Delaidelli, Hai-Feng Zhang, Sandra E. Spencer Miko, Amber K. Weiner, Alexander B. Radaoui, Rawan Shraim, Michael M. Lizardo, Christopher S. Hughes, Amy Li, Amal M. El-Naggar, Melanie Rouleau, Wei Li, Dimiter S. Dimitrov, Raushan T. Kurmasheva, Peter J. Houghton, Sharon J. Diskin, John M. Maris, Gregg B. Morin, Poul H. Sorensen
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Ewing sarcoma is the second most common bone sarcoma in children, with 1 case per 1.5 million in the United States. Although the survival rate of patients diagnosed with localized disease is approximately 70%, this decreases to approximately 30% for patients with metastatic disease and only approximately 10% for treatment-refractory disease, which have not changed for decades. Therefore, new therapeutic strategies are urgently needed for metastatic and refractory Ewing sarcoma. Experimental Design: This study analyzed 19 unique Ewing sarcoma patient- or cell line–derived xenografts (from 14 primary and 5 metastatic specimens) using proteomics to identify surface proteins for potential immunotherapeutic targeting. Plasma membranes were enriched using density gradient ultracentrifugation and compared with a reference standard of 12 immortalized non–Ewing sarcoma cell lines prepared in a similar manner. In parallel, global proteome analysis was carried out on each model to complement the surfaceome data. All models were analyzed by Tandem Mass Tags–based mass spectrometry to quantify identified proteins. Results: The surfaceome and global proteome analyses identified 1,131 and 1,030 annotated surface proteins, respectively. Among surface proteins identified, both approaches identified known Ewing sarcoma–associated proteins, including IL1RAP, CD99, STEAP1, and ADGRG2, and many new cell surface targets, including ENPP1 and CDH11. Robust staining of ENPP1 was demonstrated in Ewing sarcoma tumors compared with other childhood sarcomas and normal tissues. Conclusions: Our comprehensive proteomic characterization of the Ewing sarcoma surfaceome provides a rich resource of surface-expressed proteins in Ewing sarcoma. This dataset provides the preclinical justification for exploration of targets such as ENPP1 for potential immunotherapeutic application in Ewing sarcoma. See related commentary by Bailey, p. 934
Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease
Authors: Jamshid Maddahi, Denis Agostini, Timothy M. Bateman, Jeroen J. Bax, Rob S.B. Beanlands, Daniel S. Berman, Sharmila Dorbala, Ernest V. Garcia, James Feldman, Gary V. Heller, Juhani M. Knuuti, Pedro Martinez-Clark, Matthieu Pelletier-Galarneau, Benjamin Shepple, Nagara Tamaki, Francois Tranquart, James E. Udelson
Journal: Journal of the American College of Cardiology (2023)
Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease
Authors: Nickie N. Andescavage, Subechhya Pradhan, Alexis C. Gimovsky, Kushal Kapse, Mary T. Donofrio, Jenhao Jacob Cheng, Yushuf Sharker, David Wessel, Adre J. du Plessis, Catherine Limperopoulos
Journal: Journal of the American College of Cardiology (2023)
Implantable Cardioverter Defibrillator in Patients With Nonischemic Systolic Heart Failure With and Without Cardiac Resynchronization Therapy: Extended Follow-Up Study of the DANISH Trial
Authors: Jawad H. Butt, Adelina Yafasova, Seiko N. Doi, Jens C. Nielsen, Jens Haarbo, Hans Eiskjær, Axel Brandes, Anna M. Thøgersen, Finn Gustafsson, Christian Hassager, Jesper H. Svendsen, Dan E. Høfsten, Lars Videbæk, Christian Torp-Pedersen, Steen Pehrson, Jens Jakob Thune, Lars Køber
Journal: Circulation (2023)
10-Year Cardiovascular Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus
Authors: Christine Gyldenkerne, Martin Bødtker Mortensen, Johnny Kahlert, Pernille Gro Thrane, Kevin Kris Warnakula Olesen, Henrik Toft Sørensen, Reimar Wernich Thomsen, Michael Maeng
Journal: Journal of the American College of Cardiology (2023)